Parasites are life-forms which sustain themselves and reproduce at the expense of another organism, the host. They comprise endoparasites and ectoparasites. Parasitic worms or helminths which live inside their host feed themselves via the living host and in this way gain protection while the food absorption of the host is impaired, whereby it becomes weak and ill. The consequences of parasite infections are generally known. They cause gastroenteritis, diarrhoea, serious weight loss, colic and other disorders, sometimes resulting in death.
The endoparasites comprise parasites living inside the gastrointestinal, or in other organs, such as liver, and lungs. Ectoparasites live on the surface of the host.
They occur in humans as well as animals. Parasitic worms include the platyhelminths or flatworms, to which the cestodes or the tapeworms and the trematodes, such as liver fluke, belong, and the nematodes or the roundworms. Cestodes are segmented flatworms, trematodes are unsegmented flatworms and nematodes are cylindrical worms.
Other types of parasites that live inside the gastrointestinal tract are parasitic arthropods such as larvae of flies and mites, and protozoa. A large number of anthelmintics are already commercially available. However, the helminths develop an increasing resistance to most of the known anthelmintics. Resistance is highly disadvantageous since it results in the reduction of reproduction in livestock, other mammals and birds, and additionally results in a threat to the success of present treatment.
There are various causes for the occurrence of resistance. Resistance can inter alia occur due to changes in genes or in gene expressions, whereby the medicine can react or be modified, resulting in the loss of the activity and the survival of the helminths.
Resistance mechanisms can also occur due to the involvement of transport proteins which remove the medicines such that the medicine can no longer reach their target.
There are several reasons which lead to these resistance mechanisms. This can be due to a treatment frequency which is too high, repetitive use of the same medication regimes, or under dosing the anthelmintics. Public health authorities rely increasingly on mass medication administration programs to control parasites in both humans and animals such as livestock. They are however aware that resistance to medication can always increase and are searching for other options. In the Netherlands for instance a chemical anthelminthic for horses is still available only on veterinary prescription. The purpose here is to avoid excessive use and to avoid the occurrence of faster increasing resistance. In addition, the amount of antiparasitic medicines on the market is limited, and only a small number of new medicines are being developed.
For each chemical class of anthelmintics (imidothiazole, benzimidazole, macrocyclic lactones and others) it is the case that a resistance to one type of medicine generally brings about resistance to other types. It is possible, and is also an increasingly frequent occurrence, that there are multiple resistances wherein parasites develop sequential resistance, this irrespective of determined classes of anthelmintics. Furthermore, once a parasite is resistant to a determined population of medicines, it has never yet been the case that this population loses its resistance. When an anthelmintic class is first administered, there are only a few resistance alleles. This indicates that, if there is no treatment, resistance alleles carry with them neutral or negative reproduction fitness. Resistance is moreover an inevitable consequence of the use of medicines and the selection for resistance would depend on the relative reproduction rate assigned to the susceptibility of resistance alleles to a determined level of use of medicines.
For specific parasites and in specific situations of medicine use it may be that resistance never develops. When resistance to a medicine occurs, there are three stages linked to the accumulation of resistance alleles:                1. Resistance is generally a random event influenced by the population size and diversity; mutation rate of the genes; and the relative condition of those individuals having the mutation compared to the wild-type gene. The frequency of the resistance allele is in general fairly low.        2. The development of the resistance occurs as a response to a selective agent which kills susceptible worms but which allows those which are resistant to survive and reproduce. Treatment with the medicines is therefore a very potent means for selecting resistance alleles. If continuous selection takes place, the frequency of the resistance alleles then increases and these are spread through the population.        3. Resistance develops as soon as the selection increases progressively and increasing numbers of R-alleles occur. From this moment the parasite is found to have become resistant.        
The presence of resistant genotypes always occurs much faster than clinical resistance can be observed. Since the medicines are very often used in a dosage which is much higher than the minimum required to kill most of the worms, the selection can produce a high frequency of R-alleles before clinical resistance is observed.
Due to the fast increasing resistances occurring in helminth that is developed against a known chemical class of anthelminthics, there is a need for a new substance, which acts in a different way and belongs to another class of medicines, for combating parasites in animals as well as humans.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.